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Functional cell mediated lympholysis: II. Genetics

N E Goeken, J S Thompson

    Tissue Antigens
    |January 1, 1981
    PubMed
    Summary

    Functional Cell Mediated Lympholysis (F-CML) causes diminished lymphocyte response. Genetic studies suggest F-CML targets may be located near HLA-B, distinct from known HLA loci.

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    Area of Science:

    • Immunology
    • Human Genetics
    • Transplantation Immunology

    Background:

    • Diminished secondary stimulation response in human lymphocytes after bi-directional mixed lymphocyte culture (MLC) is observed.
    • This phenomenon, termed Functional Cell Mediated Lympholysis (F-CML), results from cytotoxic destruction of responder cells by allogeneic stimulating cells.

    Purpose of the Study:

    • To investigate the genetic basis of Functional Cell Mediated Lympholysis (F-CML).
    • To identify the specific genetic loci targeted by the cytotoxic activity in F-CML.

    Main Methods:

    • Analysis of human lymphocyte responses in bi-directional mixed lymphocyte culture (MLC).
    • Genetic studies using recombinant families and families homozygous for HLA loci (HLA-A, B, D).
    • Assessment of F-CML activity in relation to HLA matching (HLA-A, B, HLA-DR, HLA-D).

    Main Results:

    • Matching for HLA-A, B, HLA-DR, or HLA-D did not eliminate F-CML in unrelated pairs.
    • Recombinant families indicated a target locus centromeric to HLA-A and another centromeric to HLA-B.
    • Studies in a homozygous family suggested an additional F-CML target locus separate from HLA-A, B, or D.

    Conclusions:

    • The genetic targets for Functional Cell Mediated Lympholysis are not solely determined by HLA-A, B, DR, or D loci.
    • Evidence points to at least one F-CML target antigen being coded by a locus centromeric to HLA-B.
    • This locus may be distinct from HLA-D or HLA-DR, suggesting novel genetic control of F-CML.

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